The objective of this five year Mentored Clinical Scientist Development Award is to become an independent investigator in the pathogenesis, prevention, and treatment of subcortical microvascular disease in geriatric depression. The award will help the nominee develop skills in the following areas: clinical research methodology and statistics, quantitative magnetic resonance imaging (MRI) analysis, pathogenesis of cerebral small artery disease, and assessment of cognitive function and clinical manifestations of geriatric depression. These skills will be utilized to conduct a pilot study of the role of subcortical microvascular disease in geriatric depression. The study will use a case control design to compare two groups of geriatric depressed inpatients with and without high levels of subcortical microvascular disease. The specific aim is to look for differences in hypertensive burden, cognitive function, phenomenology of depression, and rate of decline in cognition and activities of daily living (ADLs). Subsidiary analyses will correlate the regional distribution of MRI hyperintensities with the pattern of cognitive dysfunction, and will evaluate the presence of apolipoprotein E4 alleles as a marker for the development of microvascular disease. The findings from this study should have important implications for prevention, prognosis, and treatment of geriatric depression associated with microvascular disease. The nominee plans to submit an RO1 level grant on subcortical microvascular disease in geriatric depression based on results obtained in the pilot study prior to the completion of the award. The nominee plans to develop a high quality morphometric imaging laboratory which will be used as a resource for a number of clinical studies in the departments of psychiatry and clinical neurosciences at Brown. The nominee further plans on assuming a leadership role in developing a post-doctoral clinical research training program in geriatric neuropsychiatry at Brown University.